| Popis: |
The US3 kinase is conserved amongst all Alphaherpesvirinae. We and others have shown that this kinase induces dramatic rearrangements of the actin cytoskeleton, including disassembly of actin stress fibers (resulting in cell rounding) and the formation of cellular projections, which are associated with increased viral spread (Favoreel et al., 2005, PNAS). For the alphaherpesvirus pseudorabies virus (PRV), we have found that the US3-induced changes in the actin cytoskeleton are mediated through p21-activated kinases (PAKs), central regulators in RhoGTPase signaling (Van den Broeke et al., 2009, PNAS). Apart from the involvement of PAKs, relatively little is known on the cellular factors that contribute to US3-mediated actin rearrangements. Cofilin, a member of the ADF/cofilin family, is a central player in actin dynamics and is known to be inactivated through phosphorylation on serine residue 3 (S3) (Moriyama et al., 1996, Genes Cells). Our aim is to investigate whether the US3 protein of the alphaherpesvirus pseudorabies virus (PRV) affects cofilin phosphorylation, and, if so, whether this contributes to the US3-mediated effects on the actin cytoskeleton. We report that US3 leads to strong cofilin dephosphorylation, which is inhibited by a PAK inhibitor, and that overexpression of a phosphomimetic cofilin variant interferes with US3-mediated actin rearrangements. |
